HOW DOES ApoE RELATE TO ALZHEIMER’S?

A number of scientific studies[1] have led to a key breakthrough in our understanding of Alzheimer’s disease. Specifically, that the presence of the apolipoprotein E epsilon-4 allele (APOE-4) is the most important genetic risk for Alzheimer’s disease.

When the APOE-4 allele is present on chromosome 19 there is an elevated risk of developing late-onset Alzheimer’s disease.

According to the National Institutes of Health[2], people who have the APOE-4 allele on chromosome 19 have an elevated risk of developing late-onset Alzheimer’s disease.  This one gene is the strongest known link between what causes individuals to develop Alzheimer’s.

The APOE gene, which is inherited (one copy from your mother and another from your father, just as for other genes), comes in three variants known as alleles, numbered 2 through 4. APOE-2 is relatively rare, and research has shown that it reduces the risk of development of Alzheimer’s. APOE3 is the most common allele, and does not increase risk for Alzheimer’s. But the epsilon-4 allele, referred to as APOE-4, present in 80 million Americans, increases risk for Alzheimer’s disease.

Inheriting the APOE-4 allele from both parents greatly increases the risk of offspring developing Alzheimer’s

About 25% of people carry APOE-4, and the gene is present in chromosome 19. For the 75% of people with no APOE-4, their lifetime risk of Alzheimer’s disease is only about 9%; with one copy it is about 30%; and with two copies, over 50%. Therefore, it is helpful to know where you stand, and to get on a prevention program if you are at risk.

The APOE gene is used by the body to create a protein called apolipoprotein E, which carries fats in molecules called lipoproteins. These lipoproteins are used to transport dietary fat and cholesterol through the bloodstream. Maintaining healthy cholesterol levels is essential for protecting the heart and circulatory system from cardiovascular diseases and damage caused by inflammation.

Research[3] has shown that the presence of the APOE-4 allele is associated with an increase in amyloid plaques, which are collections of peptides that build up in the brains of patients with Alzheimer’s disease. As Dr. Aloysius Alzheimer (the man who first identified the disease) observed, the brains of people with Alzheimer’s exhibit a buildup of protein plaques or clumps. Combined with an increase in toxic amyloid beta peptides, the amyloid plaques caused by the APOE-4 allele begin killing “non-vital” brain cells, especially those that deal with memory, resulting in the progressive destruction of the brain that leads to Alzheimer’s.

  • A buildup of protein clumps, amyloid plaques lead to a degeneration of the affected neurons.

Alzheimer’s occurs when certain receptors that monitor the brain’s nutritional, supportive, and protective needs trigger amyloid precursor proteins (APPs) to be cut by molecular scissors called proteases. APP can be cleaved into either four or two different fragments. APP that divides into two fragments supports brain connections (memory), but APP that divides into four peptides has been shown to induce loss of brain connections (loss of memory). The APOE-4 allele is associated with an increase in the APP division into the quartet of toxic fragments.

In addition, the APOE-4 allele affects many other processes, such as those that help regulate cardiovascular disease and the immune system. Therefore, the presence of APOE-4 is also related to an elevated risk of developing cardiovascular disease and inflammatory disorders.

By testing for APOE-4, your doctor can get the most important genetic information on your risk for Alzheimer’s disease. By starting an optimal program of prevention, you can take proactive steps in maintaining good health, thus lessening your chances of developing Alzheimer’s, cardiovascular disease, and autoimmune disorders.

[1] https://www.ncbi.nlm.nih.gov/pubmed/25217293

[2] https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet

[3] https://ghr.nlm.nih.gov/gene/APOE#conditions